Considering chronotype to improve hypertension management

is the dominant risk factor for cardio-vascular pathologies,

chronotype tend to get up later and are more active in the evening.The available data suggest that the eveningness chronotype is associated with elevated cardiometabolic risk rendering chronotype a prospective, yet overlooked, cardiovascular risk factor. 6ecently in eClinicalMedcine, Filippo Pigazzani and colleagues report their findings from the Chronotype sub-study of the Treatment in Morning versus Evening (TIME) study, which investigated the combined effect of timing of antihypertensive drugs and chronotype on cardiovascular outcomes in patients with arterial hypertension. 7Chronotype was assessed quantitatively by the modified Munich ChronoType Questionnaire and qualitatively by self-reporting.In line with previous literature, eveningness chronotype was associated with increased incidence of non-fatal myocardial infarction (MI) or stroke.The results showed lower incidence of non-fatal MI when the antihypertensive medication dosing time aligned with the patient's chronotype, i.e. eveningness chronotype dosed in the evening and morningness chronotype dosed in the morning.Strikingly, dosing time misalignment with chronotype was associated with increased risk for non-fatal MI.However, no effect of hypertension chronotherapy on the risk of non-fatal stroke was observed, potentially due to low non-fatal stroke incidence in the sub-study.In patients with intermediate chronotype, representing about 50% of the sub-study population, no effect of dosing time on cardiovascular events was shown.This observation corresponds with the results of the original TIME study showing no difference between evening vs morning dosing of antihypertensive drugs with respect to vascular death and non-fatal MI or stroke. 8Overall, these results suggest that chronotype assessment could improve hypertension risk stratification and management and reduce the risk of adverse cardiovascular events by better tailoring the dosing time of antihypertensive drugs.
The Chronotype sub-study which respects the patient's chronotype in terms of timing the antihypertensive medication, could refine the therapeutic approach to hypertension.However, one should take into consideration the potential pitfalls in conducting chronotherapeutic studies 9 when interpreting these findings.Interesting results of the Chronotype sub-study are warranted confirmation in larger prospective clinical trials with more diverse populations and elevated cardiovascular risk to broaden generalisability and deepen the mechanistic understanding of the chronotype-hypertension therapeutic implications.Furthermore, a more rigorously controlled selection of patients and consideration of biological time instead of arbitrary hourly time intervals could strengthen the value of the results.Additionally, use of ambulatory BP monitoring in future studies may help detect isolated office hypertension or masked hypertension and control for hemodynamic effects of therapeutic intervention.
In addition to BP, elevated heart rate and its nondipping are also significant cardiovascular risk factors that are generally neglected in hypertensive patients. 10herefore, it seems reasonable to contemplate that concurrent consideration of chronotype and circadian heart rate variations could better cardiovascular risk assessment and heart rate control in hypertension, and thus potentially improve cardiovascular prognosis.
The Chronotype sub-study provides proof-of-concept evidence that considering endogenous circadian rhythms by estimation of the hypertensive patient's chronotype could help finetune cardiovascular risk stratification and antihypertensive therapy tailoring to reduce the risk of adverse cardiovascular events.Declaration of interests DMR will receive an honoraria for coauthoring a report for the Abell Foundation on school start times in Baltimore, MD.She is currently a DEI Committee member for the Sleep Research Society, and was the Trainee Member at Large on the board of directors from 2022 to 2023.FS received honoraria for presentations from Novo Nordisk Slovakia, Egis Slovakia and Roche Slovakia.TB has no conflicts of interests to declare.

Contributors
TB and FS: conceptualisation, literature search, writing-original draft, review and editing.DMR: literature search, writing-review and editing.All authors approved the submitted version.